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Reviewed, UniProtKB/Swiss-Prot P51797 (CLCN6_HUMAN)

Last modified November 25, 2008. Version 83. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Chloride channel protein 6
      Short name=ClC-6
Gene names
Name: CLCN6
Synonyms: KIAA0046
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length869 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
Protein existenceEvidence at transcript level.

General annotation (Comments)

Function

Voltage-gated chloride channel. Chloride channels have several functions including the regulation of cell volume; membrane potential stabilization, signal transduction and transepithelial transport.

Subcellular location

Membrane; Multi-pass membrane protein.

Tissue specificity

Testis, ovary, small intestine, brain and skeletal muscle. Low level expression in aortic and coronary vascular smooth muscle cells, and aortic endothelial cells. Isoform C is only detected in kidney.

Sequence similarities

Belongs to the chloride channel (TC 2.A.49) family. [View classification]

Contains 2 CBS domains.

Alternative products

This entry describes 5 isoforms produced by alternative splicing. [Align] [Select]
Isoform A (identifier: P51797-1)

Also known as: Clc-6a;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform B (identifier: P51797-2)

Also known as: ClC-6b; D2-A1;

The sequence of this isoform differs from the canonical sequence as follows:
     237-320: DKRDFVSAGA...LLNFGEFKCS → YGKRQERLCI...APWIAELWRV
     321-869: Missing.
Isoform C (identifier: P51797-3)

Also known as: ClC-6c; D1-A1;

The sequence of this isoform differs from the canonical sequence as follows:
     319-353: CSDSDKKCHLWTAMDLGFFVVMGVIGGLLGATFNC → SLREPPCVSGNHRGGVCGLDGVRRMPTDVLFESNR
     354-869: Missing.
Isoform D (identifier: P51797-4)

Also known as: ClC-6d; D1-A2;

The sequence of this isoform differs from the canonical sequence as follows:
     237-308: DKRDFVSAGA...QFGSWGSFQL → SGCWSCCSFR...APWIAELWRV
     309-869: Missing.
Isoform E (identifier: P51797-5)

The sequence of this isoform differs from the canonical sequence as follows:
     844-869: IVGIITRHNLTYEFLQARLRQHYQTI → VSEAPALPPP...LHLRRDLRIR
Notes: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 869869Chloride channel protein 6
PRO_0000094449

Regions

Transmembrane82 – 10221 Potential
Transmembrane130 – 15021 Potential
Transmembrane184 – 20421 Potential
Transmembrane245 – 26521 Potential
Transmembrane334 – 35421 Potential
Transmembrane375 – 39521 Potential
Transmembrane462 – 48221 Potential
Transmembrane511 – 53121 Potential
Domain605 – 66258CBS 1
Domain807 – 86862CBS 2
Compositional bias4 – 1815Cys-rich

Natural variations

Alternative sequence237 – 32084DKRDF…EFKCS → YGKRQERLCISRSGCWSCCS FRGANRGYLVQSRGGFVLLE PRAHVESALLFHVCHLHPQL LPFWDSVWKLGFLPAPWIAE LWRV in isoform B.
VSP_001043
Alternative sequence237 – 30872DKRDF…GSFQL → SGCWSCCSFRGANRGYLVQS RGGFVLLEPRAHVESALLFH VCHLHPQLLPFWDSVWKLGF LPAPWIAELWRV in isoform D.
VSP_001047
Alternative sequence309 – 869561Missing in isoform D.
VSP_001048
Alternative sequence319 – 35335CSDSD…ATFNC → SLREPPCVSGNHRGGVCGLD GVRRMPTDVLFESNR in isoform C.
VSP_001045
Alternative sequence321 – 869549Missing in isoform B.
VSP_001044
Alternative sequence354 – 869516Missing in isoform C.
VSP_001046
Alternative sequence844 – 86926IVGII…HYQTI → VSEAPALPPPLREDPLARCC LCTQASHQKRRHPTRRGECG PTLALNPARLPCTRDPFPCL PADGTSVPLAVLSSQSRAST RLCLPPEMLLFTPYHWCSLV LHLRRDLRIR in isoform E.
VSP_017188
Natural variant1981G → E: dbSNP rs198400.
VAR_023051

Sequences

Sequence LengthMass (Da)Tools
Isoform A (Clc-6a) [UniParc].

Last modified October 1, 1996. Version 1.
Checksum: E4273777D9FF4328

FASTA86997,217
        10         20         30         40         50         60 
MAGCRGSLCC CCRWCCCCGE RETRTPEELT ILGETQEEED EILPRKDYES LDYDRCINDP 

        70         80         90        100        110        120 
YLEVLETMDN KKGRRYEAVK WMVVFAIGVC TGLVGLFVDF FVRLFTQLKF GVVQTSVEEC 

       130        140        150        160        170        180 
SQKGCLALSL LELLGFNLTF VFLASLLVLI EPVAAGSGIP EVKCYLNGVK VPGIVRLRTL 

       190        200        210        220        230        240 
LCKVLGVLFS VAGGLFVGKE GPMIHSGSVV GAGLPQFQSI SLRKIQFNFP YFRSDRDKRD 

       250        260        270        280        290        300 
FVSAGAAAGV AAAFGAPIGG TLFSLEEGSS FWNQGLTWKV LFCSMSATFT LNFFRSGIQF 

       310        320        330        340        350        360 
GSWGSFQLPG LLNFGEFKCS DSDKKCHLWT AMDLGFFVVM GVIGGLLGAT FNCLNKRLAK 

       370        380        390        400        410        420 
YRMRNVHPKP KLVRVLESLL VSLVTTVVVF VASMVLGECR QMSSSSQIGN DSFQLQVTED 

       430        440        450        460        470        480 
VNSSIKTFFC PNDTYNDMAT LFFNPQESAI LQLFHQDGTF SPVTLALFFV LYFLLACWTY 

       490        500        510        520        530        540 
GISVPSGLFV PSLLCGAAFG RLVANVLKSY IGLGHIYSGT FALIGAAAFL GGVVRMTISL 

       550        560        570        580        590        600 
TVILIESTNE ITYGLPIMVT LMVAKWTGDF FNKGIYDIHV GLRGVPLLEW ETEVEMDKLR 

       610        620        630        640        650        660 
ASDIMEPNLT YVYPHTRIQS LVSILRTTVH HAFPVVTENR GNEKEFMKGN QLISNNIKFK 

       670        680        690        700        710        720 
KSSILTRAGE QRKRSQSMKS YPSSELRNMC DEHIASEEPA EKEDLLQQML ERRYTPYPNL 

       730        740        750        760        770        780 
YPDQSPSEDW TMEERFRPLT FHGLILRSQL VTLLVRGVCY SESQSSASQP RLSYAEMAED 

       790        800        810        820        830        840 
YPRYPDIHDL DLTLLNPRMI VDVTPYMNPS PFTVSPNTHV SQVFNLFRTM GLRHLPVVNA 

       850        860 
VGEIVGIITR HNLTYEFLQA RLRQHYQTI 

« Hide

Isoform B (ClC-6b) (D2-A1) [UniParc].

Checksum: 6B004FDB1915E8CA
Show »

32035,934
Isoform C (ClC-6c) (D1-A1) [UniParc].

Checksum: 078E68BE3A147EB6
Show »

35338,742
Isoform D (ClC-6d) (D1-A2) [UniParc].

Checksum: 5BAE9FE7C2AD341E
Show »

30834,443
Isoform E [UniParc].

Checksum: 1FD666515C9CA2BF
Show »

953106,304

References

« Hide 'large scale' references
[1]"ClC-6 and ClC-7 are two novel broadly expressed members of the CLC chloride channel family."
Brandt S., Jentsch T.J.
FEBS Lett. 377:15-20(1995) [PubMed: 8543009] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A), TISSUE SPECIFICITY.
Tissue: Brain.
[2]"Alternative splicing of ClC-6 (a member of the ClC chloride-channel family) transcripts generates three truncated isoforms one of which, ClC-6c, is kidney-specific."
Eggermont J., Buyse G., Voets T., Tytgat J., De Smedt H., Droogmans G., Nilius B.
Biochem. J. 325:269-276(1997) [PubMed: 9224655] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS B; C AND D), NUCLEOTIDE SEQUENCE [MRNA] OF 1-409 (ISOFORM A), TISSUE SPECIFICITY.
Tissue: Chronic myeloid leukemia cell.
[3]"Complete genomic structure of the CLCN6 and CLCN7 putative chloride channel genes."
Kornak U., Boesl M.R., Kubisch C.
Biochim. Biophys. Acta 1447:100-106(1999) [PubMed: 10500249] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM A).
[4]"Prediction of the coding sequences of unidentified human genes. II. The coding sequences of 40 new genes (KIAA0041-KIAA0080) deduced by analysis of cDNA clones from human cell line KG-1."
Nomura N., Nagase T., Miyajima N., Sazuka T., Tanaka A., Sato S., Seki N., Kawarabayasi Y., Ishikawa K., Tabata S.
DNA Res. 1:223-229(1994) [PubMed: 7584044] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A).
Tissue: Bone marrow.
[5]"Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones."
Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.
DNA Res. 9:99-106(2002) [PubMed: 12168954] [Abstract]
Cited for: SEQUENCE REVISION.
[6]"The DNA sequence and biological annotation of human chromosome 1."
Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. expand/collapse author list , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
Nature 441:315-321(2006) [PubMed: 16710414] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT GLU-198.
[7]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A).
Tissue: Brain.
[8]"Expression of CLCN voltage-gated chloride channel genes in human blood vessels."
Lamb F.S., Clayton G.H., Liu B.-X., Smith R.L., Barna T.J., Schutte B.C.
J. Mol. Cell. Cardiol. 31:657-666(1999) [PubMed: 10198195] [Abstract]
Cited for: TISSUE SPECIFICITY.
Tissue: Aortic endothelium and Vascular smooth muscle.

Cross-references

Sequence databases

X83378 mRNA. Translation: CAA58292.1.
X96391 mRNA. Translation: CAA65255.1.
X99472 Genomic DNA. Translation: CAA67835.1.
X99473 mRNA. Translation: CAA67836.1.
X99474 mRNA. Translation: CAA67837.1.
X99475 mRNA. Translation: CAA67838.1.
AF009257 expand/collapse EMBL AC list , AF009247, AF009248, AF009249, AF009250, AF009251, AF009252, AF009253, AF009254, AF009255, AF009256 Genomic DNA. Translation: AAB69287.1.
D28475 mRNA. Translation: BAA05836.4.
AL953897, AL021155 Genomic DNA. Translation: CAI15891.1.
AL953897, AL021155 Genomic DNA. Translation: CAI15892.1.
AL953897, AL021155 Genomic DNA. Translation: CAI15893.1.
AL953897, AL021155 Genomic DNA. Translation: CAI15894.1.
AL953897, AL021155 Genomic DNA. Translation: CAI15895.1.
AL021155, AL953897 Genomic DNA. Translation: CAI23402.1.
AL021155, AL953897 Genomic DNA. Translation: CAI23403.1.
AL021155, AL953897 Genomic DNA. Translation: CAI23404.1.
AL021155, AL953897 Genomic DNA. Translation: CAI23405.1.
AL021155, AL953897 Genomic DNA. Translation: CAI23406.1.
BC117420 mRNA. Translation: AAI17421.1.
BC117424 mRNA. Translation: AAI17425.1.
PIRS68428.
RefSeqNP_001277.1.
NP_068503.1.
NP_068504.1.
NP_068505.1.
UniGeneHs.193043

3D structure databases

ModBaseSearch...

PTM databases

PhosphoSiteP51797.

Genome annotation databases

EnsemblENSG00000011021. Homo sapiens. [Contig view]
GeneID1185.
KEGGhsa:1185.

Organism-specific databases

H-InvDBHIX0000129.
HGNCHGNC:2024. CLCN6.
MIM602726. gene.
PharmGKBPA26551.
HUGESearch...
GenAtlasSearch...
GeneCardsSearch...

Phylogenomic databases

HOVERGENP51797.

Gene expression databases

ArrayExpressP51797.

Family and domain databases

InterProIPR014743. Cl-channel_core.
IPR001807. Cl-channel_volt.
IPR002248. Cl_channel6.
IPR000644. Cysta_beta_synth_core.
[Graphical view]
Gene3DG3DSA:1.10.3080.10. Cl-channel_core. 1 hit.
PANTHERPTHR11689. Cl-channel_volt. 1 hit.
PfamPF00571. CBS. 1 hit.
PF00654. Voltage_CLC. 1 hit.
[Graphical view]
PRINTSPR00762. CLCHANNEL.
PR01117. CLCHANNEL6.
SMARTSM00116. CBS. 2 hits.
[Graphical view]
PROSITEPS51371. CBS. 2 hits.
[Graphical view]
ProtoNetSearch...

Other Resources

NextBio4898.
SOURCESearch...

Entry information

Entry nameCLCN6_HUMAN
AccessionPrimary (citable) accession number: P51797
Secondary accession number(s): O60818 expand/collapse secondary AC list , O60819, O60820, O60821, P78520, P78521, Q17R81, Q5SNW2, Q5SNW3, Q5SNX1, Q5SNX2, Q5SNX3, Q99427, Q99428, Q99429
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: November 25, 2008
This is version 83 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

Relevant documents

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Hum